The present invention discloses a method of treating, preventing or ameliorating tumor growth by administering a therapeutic agent that selectively inhibits dipeptidyl peptidase including fibroblast activation protein and dipeptidyl peptidase 8/9 in combination with an immune checkpoint inhibitor. The method specifically discloses use of Talabostat in combination with an immune checkpoint inhibitor, its pharmaceutical composition and process of preparing such composition.

In some embodiments, the invention is directed to a method for diagnosing fibrosis and/or fibrosis related diseases and to a method for screening a pharmaceutically active compound for the treatment of fibrosis and/or fibrosis related diseases. The present invention further relates to compositions for use in the treatment, amelioration, and/or prevention of fibrosis. In certain embodiments, the compositions modulate the activity of a miRNA for the treatment, amelioration, and/or prevention of fibrosis. In certain embodiments, the compositions inhibit the activity of miR-21 for the treatment, amelioration, and/or prevention of fibrosis.

The disclosure provides biomarkers for diagnosis and monitoring of transthyretin (TTR) amyloidosis. The disclosure further provides methods for selection of agents for treatment of TTR amyloidosis using the biomarkers. The disclosure further provides kits for practicing the methods provided herein.

The present disclosure relates to methods for increasing telomere length in one or more human cells and/or increasing genome stability of one or more human cells, for example by contacting one or more human cells with an agent that increases expression of Zscan4 in the one or more human cells. Methods of treating a subject in need of telomere lengthening, treating a disease or condition associated with a genomic and/or chromosome abnormality, of rejuvenating one or more human cells, of rejuvenating tissues or organs, and of rejuvenating a subject in need thereof, for example by contacting one or more human cells in the subject with an agent that increases expression of Zscan4, or by administering to a subject in need thereof, an agent that increases expression of Zscan4 are also provided.

The compositions and methods of the invention provide compositions and methods for preferential targeting of tissues to delivery therapeutic or diagnostic agents. For example, such compounds are useful in the treatment of joint disorders those affecting articulating joints, e.g., injury-induced osteoarthritis as well as autoimmune diseases affecting joint tissue such as rheumatoid arthritis.

Provided are hybrid tRNA/pre-microRNA and tRNA molecules and their use in methods of preventing and treating hepatocellular carcinoma (HCC). In some embodiments, provided are polynucleotides that include a tRNA operably linked to one or more pre-microRNA (pre-miRNA), where the tRNA and/or pre-miRNA are operably linked to one or more inserted RNA molecules that inhibit the growth or proliferation of a hepatocellular carcinoma (HCC) cell.

Provided herein are compositions of lipid-based nanoparticles, such as exosomes, that contain a therapeutic STAT3-targeting inhibitory RNA. Also provided are methods of using such compositions to treat a patient having fibrosis or a disease associated with fibrosis.

Migration of HIV-1 infected monocytes across the endothelial barrier plays an essential role in establishing and maintenance of viral reservoir in the brain and leads to neuroinflammation, neuronal damage, and subsequent HIV-induced central nervous system (CNS) dysfunction. These processes continue despite antiretroviral therapy (ART) due to limited pharmacological permeability of the blood-brain barrier, the presence of residual viral replication, and the reactivation of latent viruses. Compositions comprising Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonucleases targeted to activated leukocytes cell adhesion molecule (ALCAM/CD166), chemotactic recruitment (CCR2/5), adhesion to the endothelium (ALCAM) and junctional diapedesis (JAM-A) achieves maximum repression of leukocyte transmigration and block of the spread of the virus to different tissues and organs.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the Transmembrane protease, serine 6 (TMPRSS6) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a TMPRSS6 gene and to methods of preventing and treating a TMPRSS6-associated disorder, e.g., a disorder associated with iron overload and/or a disorder of ineffective erythropoiesis, e.g., hereditary hemochromatosis, β-thalassemia (e.g., β-thalassemia major and β-thalassemia intermiedia), polycythemia vera, myelodysplastic syndrome, congenital dyserythropoietic anemias, pyruvate kinase deficiency, erythropoietic porphyria, Parkinson's Disease, Alzheimer's Disease or Friedreich's Ataxia.

Molecules are provided for inducing or facilitating exon skipping in forming spliced mRNA products from pre-mRNA molecules in cells. The molecules may be provided directly as oligonucleotides or expression products of vectors that are administered to a subject. High rates of skipping can be achieved. High rates of skipping reduce the severity of a disease like Duchene Muscular Dystrophy so that the disease is more like Becker Muscular Dystrophy. This is a severe reduction in symptom severity and mortality.